Hypocalcemia and inhibition of parathyroid hormone secretion after administration of WR-2721 (a radioprotective and chemoprotective agent)

Journal Article · Thu Nov 10 04:00:00 EST 1983 · N.Engl. J. Med.; (United States)

DOI:https://doi.org/10.1056/NEJM198311103091901· OSTI ID:7011611

Glover, D; Riley, L; Carmichael, K; Spar, B; Glick, J; Kligerman, M M; Agus, Z S; Slatopolsky, E; Attie, M; Goldfarb, S

The causes of the hypocalcemia associated with WR-2721, an experimental drug that protects normal tissues against the toxic effects of radiation and chemotherapy were investigated. Sixteen patients with advanced cancers had serial measurements of serum calcium and other studies of blood chemistry before and after taking the compound. In all 16 patients (18 courses) the mean serum calcium level fell from 2.33 to 1.90 mmol per liter (9.33 to 7.62 mg per deciliter, after WR-2721, and in all 8 patients from whom data were obtained, serum calcium levels remained depressed at 24 hours. In 12 patients, ionized calcium levels dropped from 0.98 to 0.80 mmol per liter. Serum magnesium values fell from 0.96 to 0.74 mmol per liter (1.91 to 1.48 mg per deciliter. There were no changes in arterial pH or serum phosphate concentrations. In nine patients urinary calcium excretion rose from 3.96 to 10.68 mumol per minute after WR-2721. Despite hypocalcemia, parathyroid hormone levels fell in all subjects. WR-2721 also inhibited the release of parathyroid hormone from bovine parathyroid cells incubated in vitro in low (0.5 mM) concentrations of calcium. The authors conclude that WR-2721 inhibits the secretion of parathyroid hormone and enhances calciuria, thereby leading to hypocalcemia.

• OSTI ID: 7011611
• Journal Information: N.Engl. J. Med.; (United States), Journal Name: N.Engl. J. Med.; (United States) Vol. 309:19; ISSN NEJMA
• Country of Publication: United States
• Language: English

Related Subjects

560306* -- Chemicals Metabolism & Toxicology-- Man-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALINE EARTH METALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BLOOD SERUM
BODY FLUIDS
CALCIUM
CLEARANCE
DRUGS
ELEMENTS
EXCRETION
HORMONES
INHIBITION
KINETICS
MAGNESIUM
MATERIALS
METALS
OXYGEN COMPOUNDS
PARATHORMONE
PATIENTS
PEPTIDE HORMONES
PHOSPHATES
PHOSPHORUS COMPOUNDS
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
URINE
WASTES